Over 30 biologically diverse sexually transmitted disease (STD) pathogens cause an estimated 250 million cases of STDs worldwide, each year. STD pathogens cause not only acute disease but also long-term sequelae, such as sterility, ectopic pregnancy and cancer. New and innovative immunological investigations can assist in understanding controlling and preventing STDs. The proposed Program Project is a collaborative effort between Johns Hopkins Medical Institutions (JHMI) and the Walter Reed Army Institute of Research (WRAIR) toward that goal. It consists of three projects built around two cores. Project 1 (Humoral Immune Response to Natural Chlamydia Infection, Raphael P. Viscidi, MD, PI) will develop reagents and assays to identify antibodies to specific chlamydial gene products in sera and in genital secretions. It will also attempt to characterize serologic markers which are predictive of a reduced risk of infection by a nested case-control study in the Baltimore City STD Clinics. Project 2 (Immune Responses to Gonococcal Infections, Carolyn D. Deal, PhD, PI) will study early host response to gonococcal infection in human male intraurethral challenge model as well as in STD clinic patients in the acute phase of infection. Serum, cervicovaginal lavage and gonococcal strain specimens collected at the time of recruitment in the nested case-control study will be examined to address the question of post-infection immunity to specific antigens. In addition, a mouse model of transient gonococcal infection will be optimized to test the ability of monoclonal antibodies to passively block transient infection and to evaluate gonococcal vaccinogens. Project 3 (T Cell Responses to HPV Oncoproteins in Cervical Carcinoma, Drew M. Pardoll, MD/PhD, PI) will initially attempt to identify MHC class 1-restricted CD8 + CTL directed against HPV-16 E6 and E7 proteins in patients who have HPV-associated pre-invasive or invasive cervical carcinoma. CTL epitopes will be mapped and the use of viral proteins in antigen-specific immunotherapy of advanced cervical cancer will be considered. The Clinical Core (Core A, Jonathan M. Zenilman, MD, PI) will be centered at the Baltimore City STD Clinics. The Coordinating Core (Core B, Keerti V. Shah, MD/DrPH, PI) will administer and coordinate the Program Project and provide biostatistical/epidemiological consultation. In summary, the Program Project will aim to elucidate protective immunological mechanisms against the pathology associated with three of the most prevalent and most important STDs.